FGF2 is overexpressed in asthma and promotes airway inflammation through the FGFR/MAPK/NF-κB pathway in airway epithelial cells.

BACKGROUND: Airway inflammation is the core pathological process of asthma, with the key inflammatory regulators incompletely defined. Recently, fibroblast growth factor 2 (FGF2) has been reported to be an inflammatory regulator; however, its role in asthma remains elusive. This study aimed to investigate the immunomodulatory role of FGF2 in asthma. METHODS: First, FGF2 expression was characterised in clinical asthma samples and the house dust mite (HDM)-induced mouse chronic asthma model. Second, recombinant mouse FGF2 (rm-FGF2) protein was intranasally delivered to determine the effect of FGF2 on airway inflammatory cell infiltration. Third, human airway epithelium-derived A549 cells were stimulated with either HDM or recombinant human interleukin-1ß (IL-1ß) protein combined with or without recombinant human FGF2. IL-1ß-induced IL-6 or IL-8 release levels were determined using enzyme-linked immunosorbent assay, and the involved signalling transduction was explored via Western blotting. RESULTS: Compared with the control groups, the FGF2 protein levels were significantly upregulated in the bronchial epithelium and alveolar areas of clinical asthma samples (6.70 ± 1.79 vs. 16.32 ± 2.40, P = 0.0184; 11.20 ± 2.11 vs. 21.00 ± 3.00, P = 0.033, respectively) and HDM-induced asthmatic mouse lung lysates (1.00 ± 0.15 vs. 5.14 ± 0.42, P < 0.001). Moreover, FGF2 protein abundance was positively correlated with serum total and anti-HDM IgE levels in the HDM-induced chronic asthma model (R2 = 0.857 and 0.783, P = 0.0008 and 0.0043, respectively). Elevated FGF2 protein was mainly expressed in asthmatic bronchial epithelium and alveolar areas and partly co-localised with infiltrated inflammatory cell populations in HDM-induced asthmatic mice. More importantly, intranasal instillation of rm-FGF2 aggravated airway inflammatory cell infiltration (2.45 ± 0.09 vs. 2.88 ± 0.14, P = 0.0288) and recruited more subepithelial neutrophils after HDM challenge [(110.20 ± 29.43) cells/mm2 vs. (238.10 ± 42.77) cells/mm2, P = 0.0392] without affecting serum IgE levels and Th2 cytokine transcription. In A549 cells, FGF2 was upregulated through HDM stimulation and promoted IL-1ß-induced IL-6 or IL-8 release levels (up to 1.41 ± 0.12- or 1.44 ± 0.14-fold change vs. IL-1ß alone groups, P = 0.001 or 0.0344, respectively). The pro-inflammatory effect of FGF2 is likely mediated through the fibroblast growth factor receptor (FGFR)/mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) pathway. CONCLUSION: Our findings suggest that FGF2 is a potential inflammatory modulator in asthma, which can be induced by HDM and acts through the FGFR/MAPK/NF-κB pathway in the airway epithelial cells.

A colorimetric and fluorescence turn-on probe for the detection of palladium in aqueous solution and its application in vitro and in vivo.

Palladium has attracted a growing number of attention due to its widely application and environmental toxicity. Consequently, a novel colorimetric and fluorescent turn-on probe (NT-Pd) was designed for sensing of palladium. This probe was capable of detecting palladium in aqueous solution (DMSO was less than 1%, v/v). Under this mild condition, NT-Pd displayed high selectivity and sensitivity for sensing of palladium in both colorimetric and fluorescent strategy, such as low detection limit (5.30 nM) and rapid response time (within 10 min). In addition, NT-Pd was successfully applied for imaging of exogenous palladium in living cells and zebrafishes with good biocompatibility and low toxicity, indicating this probe has satisfactory application potential to track palladium in the complicated biological system.

The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status.

An acute respiratory disease, caused by a novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV), the coronavirus disease 2019 (COVID-19) has spread throughout China and received worldwide attention. On 30 January 2020, World Health Organization (WHO) officially declared the COVID-19 epidemic as a public health emergency of international concern. The emergence of SARS-CoV-2, since the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century. As of 1 March 2020, a total of 87,137 confirmed cases globally, 79,968 confirmed in China and 7169 outside of China, with 2977 deaths (3.4%) had been reported by WHO. Meanwhile, several independent research groups have identified that SARS-CoV-2 belongs to ß-coronavirus, with highly identical genome to bat coronavirus, pointing to bat as the natural host. The novel coronavirus uses the same receptor, angiotensin-converting enzyme 2 (ACE2) as that for SARS-CoV, and mainly spreads through the respiratory tract. Importantly, increasingly evidence showed sustained human-to-human transmission, along with many exported cases across the globe. The clinical symptoms of COVID-19 patients include fever, cough, fatigue and a small population of patients appeared gastrointestinal infection symptoms. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Currently, there are few specific antiviral strategies, but several potent candidates of antivirals and repurposed drugs are under urgent investigation. In this review, we summarized the latest research progress of the epidemiology, pathogenesis, and clinical characteristics of COVID-19, and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus.

Regulation of Androgen Receptor Expression Alters AMPK Phosphorylation in the Endometrium: In Vivo and In Vitro Studies in Women with Polycystic Ovary Syndrome.

The failure of reproductive success in polycystic ovary syndrome (PCOS) patients could be in part due to endometrial dysfunction. However, no studies have investigated any causality between androgen, androgen receptor (AR) expression, and adenosine monophosphate activated protein kinase (AMPK) activation in the endometrium under physiological and pathological conditions. In the present study, we show that 1) endometrial AR expression levels fluctuate in non-PCOS and PCOS patients during the menstrual cycle; 2) the menstrual phase-dependent alteration of p-AMPKα expression occurs in non-PCOS patients but not in PCOS patients; 3) AR expression is higher in PCOS patients than non-PCOS patients during hyperplasia while AMPKα activation (indicated by the ratio of p-AMPKα to AMPKα); and 4) co-localization of AR and Ki-67 in epithelial cell nuclei is observed in endometrial hyperplasia. Importantly, using in vitro human tissue culture and an in vivo 5α-dihydrotestosterone-treated rat model, we show that the action of androgen on AMPKα activation is likely mediated through nuclear AR, especially in epithelial cells. Collectively, we present evidence that AR expression and AMPKα activation depend on menstrual cycle phase and the presence of PCOS, and the data suggest that AR-mediated regulation of AMPKα activation might play a role in the development of endometrial hyperplasia.

Reversing the reduced level of endometrial GLUT4 expression in polycystic ovary syndrome: a mechanistic study of metformin action.

Conflicting results have been reported regarding whether or not insulin-regulated glucose transporter 4 (GLUT4) is expressed in human and rodent endometria. There is an inverse relationship between androgen levels and insulin-dependent glucose metabolism in women. Hyperandrogenemia, hyperinsulinemia, and insulin resistance are believed to contribute to endometrial abnormalities in women with polycystic ovary syndrome (PCOS). However, it has been unclear in previous studies if endometrial GLUT4 expression is regulated by androgen-dependent androgen receptors (ARs) and/or the insulin receptor/Akt/mTOR signaling network. In this study, we demonstrate that GLUT4 is expressed in normal endometrial cells (mainly in the epithelial cells) and is down-regulated under conditions of hyperandrogenemia in tissues from PCOS patients and in a 5α-dihydrotestosterone-induced PCOS-like rat model. Western blot analysis revealed reduced endometrial GLUT4 expression and increased AR expression in PCOS patients. However, the reduced GLUT4 level was not always associated with an increase in AR in PCOS patients when comparing non-hyperplasia with hyperplasia. Using a human tissue culture system, we investigated the molecular basis by which GLUT4 regulation in endometrial hyperplasia tissues is affected by metformin in PCOS patients. We show that specific endogenous organic cation transporter isoforms are regulated by metformin, and this suggests a direct effect of metformin on endometrial hyperplasia. Moreover, we demonstrate that metformin induces GLUT4 expression and inhibits AR expression and blocks insulin receptor/PI3K/Akt/mTOR signaling in the same hyperplasia human tissues. These findings indicate that changes in endometrial GLUT4 expression in PCOS patients involve the androgen-dependent alteration of AR expression and changes in the insulin receptor/PI3K/Akt/mTOR signaling network.

[Epidemiological survey and risk factor analysis of asthma in children in urban districts of Zhengzhou, China].

OBJECTIVE: To study the epidemiological features, treatment status, and risk factors for asthma in children in Zhengzhou, China. METHODS: Questionnaires for primary screening were issued using the method of multi-stage stratified sampling. Suspected asthmatic children were given a second questionnaire, physical examination, medical history review, and auxiliary examination to confirm the diagnosis. Age- and sex-matched non-asthmatic children were randomly recruited to the control group. RESULTS: The number of valid questionnaires was 10 616 (5 444 males and 5 172 females). There were 308 confirmed asthma cases and the overall prevalence was 2.90%. The prevalence in boys was higher than that in girls (3.4% vs 2.4%). The prevalence in children under 3 years of age was 10.2%, which was higher than that in other age groups. The top three triggers for asthma attack in children were respiratory infection (94.2%), weather changes (89.0%), and exercise (35.1%). The most common asthma attack was moderate (71.8%), followed by mild (22.7%). Inhaled corticosteroids, systemic corticosteroids, and antibiotics were applied to 94.8% (292 cases), 74.7% (230 cases), and 90.9% (280 cases) of all patients, respectively. Multivariate logistic regression analysis indicated the following major risk factors for asthma: history of allergic rhinitis (OR=150.285, 95% CI: 31.934-707.264), history of eczema (OR=10.600, 95% CI: 1.054-106.624), history of atopic dermatitis (OR=31.368, 95% CI: 3.339-294.683), food allergies (OR=27.373, 95% CI: 2.670-280.621), method of birth (OR=2.853, 95% CI: 1.311-6.208), age of first antibiotic use (OR=0.384, 95% CI: 0.172-0.857), frequency of antibiotic use within 1 year of age (OR=9.940, 95% CI: 6.246-15.820), use of wall decorating materials (OR=2.108, 95% CI: 1.464-3.036), and use of heat supply in winter (OR=6.046, 95% CI: 1.034-35.362). CONCLUSIONS: The prevalence of childhood asthma is associated with age and gender in Zhengzhou. Most asthma attacks are moderate, often triggered by respiratory infection. Treatment of asthma has been standardized, but still needs further improvement. History of allergic rhinitis, eczema, atopic dermatitis and food allergies, cesarean delivery, frequent use of antibiotics within 1 year of age, use of decorating materials on the wall, and use of heating in winter may increase risk for asthma, and use of antibiotics in older age is a protective factor against asthma in children.

Analyzing and modeling rheological behavior of liver fibrosis in rats using shear viscoelastic moduli.

The process of liver fibrosis changes the rheological properties of liver tissue. This study characterizes and compares liver fibrosis stages from F0 to F4 in rats in terms of shear viscoelastic moduli. Here two viscoelastic models, the Zener model and Voigt model, were applied to experimental data of rheometer tests and then values of elasticity and viscosity were estimated for each fibrosis stage. The results demonstrate that moderate fibrosis (≤F2) has a good correlation with liver viscoelasticity. The mean Zener elasticity E1 increases from (0.452±0.094) kPa (F0) to (1.311±0.717) kPa (F2), while the mean Voigt elasticity E increases from (0.618±0.089) kPa (F0) to (1.701±0.844) kPa (F2). The mean Zener viscosity increases from (3.499±0.186) Pa·s (F0) to (4.947±1.811) Pa·s (F2) and the mean Voigt viscosity increases from (3.379±0.316) Pa·s (F0) to (4.625±1.296) Pa·s (F2). Compared with viscosity, the elasticity shows smaller variations at stages F1 and F2 no matter what viscoelastic model is used. Therefore, the estimated elasticity is more effective than viscosity for differentiating the fibrosis stages from F0 to F2.

Combination of Diane-35 and Metformin to Treat Early Endometrial Carcinoma in PCOS Women with Insulin Resistance.

BACKGROUND: Young women with polycystic ovary syndrome (PCOS) have a high risk of developing endometrial carcinoma. There is a need for the development of new medical therapies that can reduce the need for surgical intervention so as to preserve the fertility of these patients. The aim of the study was to describe and discuss cases of PCOS and insulin resistance (IR) women with early endometrial carcinoma while being co-treated with Diane-35 and metformin. METHODS: Five PCOS-IR women who were scheduled for diagnosis and therapy for early endometrial carcinoma were recruited. The hospital records and endometrial pathology reports were reviewed. All patients were co-treated with Diane-35 and metformin for 6 months to reverse the endometrial carcinoma and preserve their fertility. Before, during, and after treatment, endometrial biopsies and blood samples were obtained and oral glucose tolerance tests were performed. Endometrial pathology was evaluated. Body weight (BW), body mass index (BMI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), sex hormone-binding globulin (SHBG), free androgen index (FAI), insulin area under curve (IAUC), and homeostasis model assessment of insulin resistance (HOMA-IR) were determined. RESULTS: Clinical stage 1a, low grade endometrial carcinoma was confirmed before treatment. After 6 months of co-treatment, all patients showed normal epithelia. No evidence of atypical hyperplasia or endometrial carcinoma was found. Co-treatment resulted in significant decreases in BW, BMI, TT, FAI, IAUC, and HOMA-IR in parallel with a significant increase in SHBG. There were no differences in the FSH and LH levels after co-treatment. CONCLUSIONS: Combined treatment with Diane-35 and metformin has the potential to revert the endometrial carcinoma into normal endometrial cells in PCOS-IR women. The cellular and molecular mechanisms behind this effect merit further investigation.

Preliminary study on the effect of stiffness on lamb wave propagation in bovine corneas.

The viscoelastic properties of human cornea could provide valuable information for various clinical applications. Particularly, it will be helpful to achieve a patient-specific biomechanical optimization in LASIK refractive surgery, early detection of corneal ecstatic disease or improved accuracy of intraocular pressure (IOP) measurement. However, there are few techniques that are capable of accurately assessing the corneal elasticity in situ in a nondestructive fashion. In order to develop a quantitative method for assessing both elasticity and viscosity of the cornea, we use ultrasound radiation force to excite Lamb waves in cornea, and a pulse echo transducer to track the tissue vibration. The fresh postmortem bovine eyes were treated via collagen cross-linking to make the cornea stiff. The effect of stiffness was studied by comparing the propagation of Lamb waves in normal and treated corneas. It was found that the waveform of generated Lamb waves changed significantly due to the increase in higher modes in treated corneas. This result indicated that the generated waveform was a complex of multiple harmonics and the varied stiffness will affect the energy distribution over different components. Therefore, it is important for assessing the viscoelastic properties of the cornea to know the components of Lamb wave and calculate the phase velocity appropriately.

In-vitro quantification of rat liver viscoelasticity with shear wave dispersion ultrasound vibrometry.

As a new imaging method for tissue mechanical properties, ultrasound elastography has always been the research focus in the field of medical ultrasound imaging ever since it has been proposed. This paper developed an ultrasound viscoelasticity measurement system based on shear wave dispersion ultrasound vibrometry (SDUV). This system applied acoustic radiation force to excite harmonic vibration in soft tissue. The propagation of the shear wave induced by the vibration was detected and the tissue viscoelasticity properties were calculated. Based on this system, rat livers were measured in vitro. The results shows that the system can measure the viscoelasticity reliably, offering a potential alternative to diagnosis of liver fibrosis.

[Analysis of pathological type and clinical features of lymphoma cell leukemia].

OBJECTIVE: To analyze the pathological type and clinical features of patients with lymphoma cell leukemia (LML). METHODS: According to the 2008 WHO classification of tumors of hematopoietic and lymphoid tissue, the pathological type and clinical features of 127 LML cases were analyzed retrospectively. RESULTS: There were 15 kinds of NHL developed LML. The incidence in frequent order of them was B-lymphoblastic lymphoma, CLL/small lymphocytic lymphoma (SLL) and T-lymphoblastic lymphoma. The LML of T and B cell subtypes were 45 and 74, respectively. There was a significant difference in overall survival between T-LML and B-LML (P < 0.01). Eighty one patients presented LML at the same time of the NHL diagnosis and 46 during the course (1 - 88 months) of disease. Primary nodal and extranodal NHLs developed LML were 96 and 31 cases, respectively. The clinical manifestations of LBL and SLL patients differed from that of ALL and CLL patients. CONCLUSION: LML is not a rare manifestation of NHL. Pathological types of NHL developed LML are 15 kinds in our patients. The clinical features of LML patients are somewhat special, especially for primary extranodal LML patients.